We propose to augment conditioning therapy prior to autologous transplant for Hodgkin lymphoma by adding tumor-specific radio-immuno-therapy (RIT). We have developed and procured an IND for Yttrium-90 (90Y)-labeled basiliximab, a first-in-human RIT reagent targeted to the CD25 antigen, also known as the interleukin-2 receptor a-subunit. CD25 is highly expressed on the Reed-Sternberg and associated polyclonal T cells in Hodgkin lymphoma, but is found on fewer than 5% of resting T and B cells. We have opened a Phase I trial to test this reagent combined with the BEAM conditioning regimen (BCNU, Etoposide, Ara-C, Melphalan) in patients with advanced stage, relapsed or refractory Hodgkin lymphoma. The significance of the approach evolves from the urgent need for safe, effective salvage options in these poor prognosis disease populations. Since Hodgkin patients are often young adults, we propose to intensify and target therapy, while minimizing long-term toxicities that might continue for decades in survivors. This innovative trial is first-in-human, with respect to both the use of the particular labeled antibody (basiliximab versus daclizumab), and the extension of RIT pre-transplant conditioning to Hodgkin lymphoma. Specific Aim 1: Establish appropriate dosing and safety of 90Y-basiliximab combined with BEAM conditioning for autologous transplant in patients with relapsed/refractory Hodgkin lymphoma. This is a phase I safety study using a modified rolling 6 design. Dose escalation will select the highest of 4 doses that is tolerable, with acceptable dosimetry to vital organs as the maximum tolerated dose (MTD). Additional patients will be accrued at the MTD, bringing the total to 12 at MTD. Patients with advanced stage, relapsed or refractory Hodgkin lymphoma will be treated with doses ranging from 0.3 to 0.6 mCi/kg of 90Y-basiliximab, 7 days prior to initiation of standard BEAM conditioning and AHCT. The primary objective is to establish a safe and tolerable dose for phase II trials and the primary endpoint is dose-limiting toxicity. Specific Aim 2: Describe the bi-distribution and pharmacokinetics of 90Y-basiliximab. Biodistribution and pharamaco-kinetic studies will provide information to optimize RIT administration and patient selection. Based on information obtained in this trial, we will plan to follow with a multi-center phase II trial in Hodgkin lymphoma as well as a phase I/II trial in T cell non-Hodgkin lymphoma.